1. Field of the Invention
The present invention relates to a peritoneal dialysis instrument for improving dialysis efficacy in removing excess liquid and uremic toxin by maintaining polymer osmotic agents in place of glucose in a recirculation line without requiring outside contact for the therapy of chronicle renal failure disease.
2. Description of the Related Art
Peritoneal dialysis has been applied as an effective therapy for renal failure patients. The dialysis is performed so that dialysate is infused into the peritoneal cavity from the dialysate bag through a catheter, which is implanted in the patient""s peritoneal cavity, and the dialysate is stored in the cavity for a certain time. Then, the dialysate is drained out through the same catheter. This procedure is repeated a few times a day.
This dialysis has a few advantages over hemodialysis from a physiological point of view, as it purifies blood continuously through the patients"" peritoneum, while hemodialysis uses artificial membranes. Also, peritoneal dialysis enables the patients to participate in social activity, and as a result, the dialysis has been widely applied.
In hemodialysis, ultrafiltration is achieved by raising the pressure of the blood line over that of the dialysate line. However, the same method can not be applied to peritoneal dialysis. As a result, an osmotic agent is added into the dialysate so as to raise the osmotic pressure of the dialysate over that of plasma, and the dialysate is infused into the peritoneal cavity so as to contact it to the peritoneum for removing excess liquid from the patient""s body. For this purpose, glucose has been used as an osmotic agent. However, adverse effects such as the disfunctioning of the, peritoneum due to the absorption of such a large quantity of the osmotic agent into the patient body are now recognized as a serious problem.
For solving the aforementioned problem, the inventor of the present invention has proposed an instrument and a method by which serum protein, such as albumin, globulin and the like which are permeated out through peritoneum into the dialysate, is recovered and refined, and is then concentrated and reused with dialysate as the most physiological substitutes of glucose.
In these proposed processes, the following were disclosed:
(A) A method to dissolve the recovered and refined protein in dialysate after which low molecular weight uremic toxin substances not higher than 30,000 daltons are removed by the repeated concentration/dilution procedures with a semipermeable membrane, and to reuse it as a substitute of glucose. (Japanese Laid Open Patent Application Hei 9-327511)
(B) A method to keep the abovementioned device and the components disinfected. (Japanese Laid Open Patent Application Hei 10-85324)
(C) A method to separate the malignant solute in the solvent and refine the protein by acidifying the protein and then de-acidifying it through water dialysis so as to deposit it at iso-electric pH (Japanese Laid Open Patent Application Hei 9-302388)
Also, for carrying out the invention (C), it was disclosed that the device comprises the followings:
(D) An inflow line having a filter whose maximum pore size is 100-300 nanometers for preventing bacteria invasion into the peritoneal cavity; and
(E) A two step prefilter having a pore size between 5 and 200 microns to remove blood cells, peritoneum mesothelial cells, fibrin and the like suspended in the effluent when it is drained out from peritoneal cavity.
A few attempts have been reported to utilize serum protein in ascites (Hwang, E. R., Richard, D. O. Sherman, A. et al., Dialytic Ascites Ultra-filtration in Refractory Ascites, Am. J. Gastroenteral, 77(9): 652-654, 1982, for example)
However, they did not refer to removing uremic toxin, because their target was not a renal failure patient.
Also, a method to add a peritoneum protecting component of a molecular weight of not higher than 3,000 daltons recovered from peritoneal dialysis effluent into dialysate (Japanese Laid Open Patent Application Hei 8-337590). However the recovery and reuse of the component of the molecular weight higher than 3,000 daltons is not suggested.
When plasma protein that is permeated out of the patient body is reused as an osmotic agent in place of glucose, the following conditions need to be satisfied:
(I) To minimize the contact with atmosphere and foreign matters so as to not denature the protein;
(II) To minimize plugging the semi-permeable membrane on the recirculation line, and to decrease the frequency of exchange; and
(III) To completely prevent the invasion of pathogenic bacteria and endotoxin.
For the solution of the aforementioned (I) problem, it may be suggested that a filter is set at the exit of the catheter, or, as a further perfect protection, a hollow fiber type semi-permeable membrane is set in a peritoneal cavity in order to keep the polymer in the peritoneal cavity. However, in those cases, complicated preventive means are required to avoid plugging of the membrane, and the exchange of the filter requires skillful care.
The present invention has developed a practical method and an instrument for solving the aforementioned problems, by the combination of either one of the following technologies:
[I] The drained dialysate is warmed up to a preset temperature, and then it is filtered through a prefilter for removing foreign materials so as to prevent the plugging of the filter.
[II] A semi-permeable membrane (having a cut-off point of up to 30,000 dalton) filter is used for removing uremic toxin of low molecular weight and of middle molecular weight.
[III] A supplemental electrolyte solution is supplied through a semi-permeable membrane filter (having a cut-off point of up to 5,000 dalton) for preventing the infection and invasion of endotoxin.
Also, the present inventor has found that by the use of the device, dialysate may be drained out of the peritoneal cavity and may be recirculated in a closed line. In addition, a portion of the dialysate may be filtered out through a semi-permeable membrane to remove malignant component, and then, a fresh dialysate may be supplemented through a semipermeable membrane and returned automatically into the peritoneal cavity.
Briefly, the present invention relates to an instrument-that comprises (a) a prefilter, (b) a first filter that comprises a semi-permeable membrane having a maximum permeable molecule of up to 30,000 dalton, (c) a pump to lower the outside pressure of the first filter (b) relative to the inside pressure, (d) a second filter that comprises a semi-permeable membrane having a maximum permeable molecule of 5,000 dalton, (e) and a pump to raise the pressure of a supplemental liquor line relative to the inside line of the second filter.
Also, the present invention relates to a method characterized in that dialysate is drained out of the peritoneal cavity and recirculated in a closed line, and a portion of the dialysate is filtered out through a semi-permeable membrane. Then, an equivalent volume of fresh dialysate is supplemented through a semi-permeable membrane having a maximum permeable molecule of 5,000 dalton and is then returned into the peritoneal cavity.
As a favorable embodiment for carrying out the present invention, the following technologies may be adapted:
(1) A bacteria-free filter (having a maximum pore size of 100-300 nanometers) is set up on the peritoneal cavity side of the inflow line""s joint.
(2) Dialysate in the peritoneal cavity is recirculated through a perfectly closed and continuously connected and previously disinfected line for keeping the protein not denatured in the automatic dialysate recirculation instrument.
(3) A reverse flow prevention valve (anti-reverse flow valve) is set up on the withdrawn line.
(4) A closed chamber, of which the inside can not directly be contacted by fingers, is set up for disconnection and connection procedure by remote operation from outside, after the infusion of dialysate for the daytime cycle before getting up in the morning.